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Protein

Arachidonate 15-lipoxygenase

Gene

ALOX15

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Non-heme iron-containing dioxygenase that catalyzes the stereo-specific peroxidation of free and esterified polyunsaturated fatty acids generating a spectrum of bioactive lipid mediators. Converts arachidonic acid into 12-hydroperoxyeicosatetraenoic acid/12-HPETE and 15-hydroperoxyeicosatetraenoic acid/15-HPETE. Also converts linoleic acid to 13-hydroperoxyoctadecadienoic acid. May also act on (12S)-hydroperoxyeicosatetraenoic acid/(12S)-HPETE to produce hepoxilin A3. Probably plays an important role in the immune and inflammatory responses. Through the oxygenation of membrane-bound phosphatidylethanolamine in macrophages may favor clearance of apoptotic cells during inflammation by resident macrophages and prevent an autoimmune response associated with the clearance of apoptotic cells by inflammatory monocytes. In parallel, may regulate actin polymerization which is crucial for several biological processes, including macrophage function. May also regulate macrophage function through regulation of the peroxisome proliferator activated receptor signaling pathway. Finally, it is also involved in the cellular response to IL13/interleukin-13. In addition to its role in the immune and inflammatory responses, may play a role in epithelial wound healing in the cornea maybe through production of lipoxin A4. May also play a role in endoplasmic reticulum stress response and the regulation of bone mass.2 Publications

Catalytic activityi

Arachidonate + O2 = (5Z,8Z,10E,14Z)-(12S)-12-hydroperoxyicosa-5,8,10,14-tetraenoate.1 Publication
Arachidonate + O2 = (5Z,8Z,11Z,13E)-(15S)-15-hydroperoxyicosa-5,8,11,13-tetraenoate.2 Publications

Cofactori

Fe cationPROSITE-ProRule annotationNote: Binds 1 Fe cation per subunit.PROSITE-ProRule annotation

Enzyme regulationi

Activity is increased by binding phosphatidylinositol phosphates, especially phosphatidylinositol 3,4-bisphosphate and phosphatidylinositol 4,5-bisphosphate.1 Publication

Pathwayi: hydroperoxy eicosatetraenoic acid biosynthesis

This protein is involved in the pathway hydroperoxy eicosatetraenoic acid biosynthesis, which is part of Lipid metabolism.
View all proteins of this organism that are known to be involved in the pathway hydroperoxy eicosatetraenoic acid biosynthesis and in Lipid metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi360Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi365Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi540Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi544Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi662Iron; via carboxylate; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDioxygenase, Oxidoreductase
Biological processFatty acid metabolism, Lipid metabolism
LigandCalcium, Iron, Lipid-binding, Metal-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS08621-MONOMER
BRENDAi1.13.11.33 2681
ReactomeiR-HSA-2142691 Synthesis of Leukotrienes (LT) and Eoxins (EX)
R-HSA-2142712 Synthesis of 12-eicosatetraenoic acid derivatives
R-HSA-2142770 Synthesis of 15-eicosatetraenoic acid derivatives
R-HSA-6785807 Interleukin-4 and 13 signaling
R-HSA-9018677 Biosynthesis of DHA-derived SPMs
R-HSA-9018681 Biosynthesis of protectins
R-HSA-9018896 Biosynthesis of E-series 18(S)-resolvins
R-HSA-9023661 Biosynthesis of E-series 18(R)-resolvins
R-HSA-9025106 Biosynthesis of DPAn-6 SPMs
R-HSA-9026286 Biosynthesis of DPAn-3-derived protectins and resolvins
SABIO-RKiP16050
SIGNORiP16050
UniPathwayiUPA00881

Chemistry databases

SwissLipidsiSLP:000000667

Names & Taxonomyi

Protein namesi
Recommended name:
Arachidonate 15-lipoxygenase (EC:1.13.11.332 Publications)
Short name:
15-LOX
Short name:
15-LOX-1
Alternative name(s):
12/15-lipoxygenase
Arachidonate 12-lipoxygenase, leukocyte-type (EC:1.13.11.311 Publication)
Short name:
12-LOX
Arachidonate omega-6 lipoxygenase
Gene namesi
Name:ALOX15
Synonyms:LOG15
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000161905.12
HGNCiHGNC:433 ALOX15
MIMi152392 gene
neXtProtiNX_P16050

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Lipid droplet, Membrane

Pathology & Biotechi

Involvement in diseasei

Disease susceptibility may be associated with variations affecting the gene represented in this entry. Met at position 560 may confer interindividual susceptibility to coronary artery disease (CAD) (PubMed:17959182).1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi418M → V: Catalyzes 15- and 12-lipoxygenation. 1 Publication1

Organism-specific databases

DisGeNETi246
OpenTargetsiENSG00000161905
PharmGKBiPA48

Chemistry databases

ChEMBLiCHEMBL2903
DrugBankiDB08492 (2E)-3-(2-OCT-1-YN-1-YLPHENYL)ACRYLIC ACID
GuidetoPHARMACOLOGYi1388

Polymorphism and mutation databases

BioMutaiALOX15
DMDMi126396

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved2 Publications
ChainiPRO_00002206972 – 662Arachidonate 15-lipoxygenaseAdd BLAST661

Proteomic databases

PaxDbiP16050
PeptideAtlasiP16050
PRIDEiP16050

PTM databases

iPTMnetiP16050
PhosphoSitePlusiP16050

Expressioni

Tissue specificityi

Detected in monocytes and eosinophils (at protein level). Expressed in airway epithelial cells.2 Publications

Inductioni

Up-regulated by UV-irradiation.1 Publication

Gene expression databases

BgeeiENSG00000161905
CleanExiHS_ALOX15
ExpressionAtlasiP16050 baseline and differential
GenevisibleiP16050 HS

Organism-specific databases

HPAiCAB004962
CAB004963
HPA013859

Interactioni

Subunit structurei

Interacts with PEBP1; in response to IL13/interleukin-13, prevents the interaction of PEBP1 with RAF1 to activate the ERK signaling cascade.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
PEBP1P300863EBI-14035397,EBI-716384

Protein-protein interaction databases

BioGridi106747, 4 interactors
DIPiDIP-60388N
IntActiP16050, 2 interactors
STRINGi9606.ENSP00000293761

Chemistry databases

BindingDBiP16050

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ABTmodel-A2-662[»]
ProteinModelPortaliP16050
SMRiP16050
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 114PLATPROSITE-ProRule annotationAdd BLAST113
Domaini115 – 662LipoxygenasePROSITE-ProRule annotationAdd BLAST548

Domaini

The PLAT domain can bind calcium ions; this promotes association with membranes.By similarity

Sequence similaritiesi

Belongs to the lipoxygenase family.Curated

Phylogenomic databases

eggNOGiENOG410IKAN Eukaryota
ENOG410YN4N LUCA
GeneTreeiENSGT00550000074415
HOVERGENiHBG005150
InParanoidiP16050
KOiK00460
OMAiLTCWKDL
OrthoDBiEOG091G04A4
PhylomeDBiP16050
TreeFamiTF105320

Family and domain databases

InterProiView protein in InterPro
IPR000907 LipOase
IPR013819 LipOase_C
IPR036226 LipOase_C_sf
IPR020834 LipOase_CS
IPR020833 LipOase_Fe_BS
IPR001885 LipOase_mml
IPR001024 PLAT/LH2_dom
IPR036392 PLAT/LH2_dom_sf
PANTHERiPTHR11771 PTHR11771, 1 hit
PfamiView protein in Pfam
PF00305 Lipoxygenase, 1 hit
PF01477 PLAT, 1 hit
PRINTSiPR00087 LIPOXYGENASE
PR00467 MAMLPOXGNASE
SMARTiView protein in SMART
SM00308 LH2, 1 hit
SUPFAMiSSF48484 SSF48484, 1 hit
SSF49723 SSF49723, 1 hit
PROSITEiView protein in PROSITE
PS00711 LIPOXYGENASE_1, 1 hit
PS00081 LIPOXYGENASE_2, 1 hit
PS51393 LIPOXYGENASE_3, 1 hit
PS50095 PLAT, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P16050-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MGLYRIRVST GASLYAGSNN QVQLWLVGQH GEAALGKRLW PARGKETELK
60 70 80 90 100
VEVPEYLGPL LFVKLRKRHL LKDDAWFCNW ISVQGPGAGD EVRFPCYRWV
110 120 130 140 150
EGNGVLSLPE GTGRTVGEDP QGLFQKHREE ELEERRKLYR WGNWKDGLIL
160 170 180 190 200
NMAGAKLYDL PVDERFLEDK RVDFEVSLAK GLADLAIKDS LNVLTCWKDL
210 220 230 240 250
DDFNRIFWCG QSKLAERVRD SWKEDALFGY QFLNGANPVV LRRSAHLPAR
260 270 280 290 300
LVFPPGMEEL QAQLEKELEG GTLFEADFSL LDGIKANVIL CSQQHLAAPL
310 320 330 340 350
VMLKLQPDGK LLPMVIQLQL PRTGSPPPPL FLPTDPPMAW LLAKCWVRSS
360 370 380 390 400
DFQLHELQSH LLRGHLMAEV IVVATMRCLP SIHPIFKLII PHLRYTLEIN
410 420 430 440 450
VRARTGLVSD MGIFDQIMST GGGGHVQLLK QAGAFLTYSS FCPPDDLADR
460 470 480 490 500
GLLGVKSSFY AQDALRLWEI IYRYVEGIVS LHYKTDVAVK DDPELQTWCR
510 520 530 540 550
EITEIGLQGA QDRGFPVSLQ ARDQVCHFVT MCIFTCTGQH ASVHLGQLDW
560 570 580 590 600
YSWVPNAPCT MRLPPPTTKD ATLETVMATL PNFHQASLQM SITWQLGRRQ
610 620 630 640 650
PVMVAVGQHE EEYFSGPEPK AVLKKFREEL AALDKEIEIR NAKLDMPYEY
660
LRPSVVENSV AI
Length:662
Mass (Da):74,804
Last modified:January 23, 2007 - v3
Checksum:i9ACF7FE7863A045C
GO
Isoform 2 (identifier: P16050-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     46-84: Missing.

Note: No experimental confirmation available.
Show »
Length:623
Mass (Da):70,108
Checksum:i71B99C6D8E707189
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti46E → V in AAC52118 (PubMed:9700053).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01874690D → H1 PublicationCorresponds to variant dbSNP:rs11568142Ensembl.1
Natural variantiVAR_035036102G → V. Corresponds to variant dbSNP:rs41439950Ensembl.1
Natural variantiVAR_018747103N → K1 PublicationCorresponds to variant dbSNP:rs11568099Ensembl.1
Natural variantiVAR_018748205R → Q1 PublicationCorresponds to variant dbSNP:rs11568101Ensembl.1
Natural variantiVAR_035037239V → M. Corresponds to variant dbSNP:rs3892408Ensembl.1
Natural variantiVAR_035038461A → P1 PublicationCorresponds to variant dbSNP:rs17852628Ensembl.1
Natural variantiVAR_035039560T → M Loss of catalytic activity. 1 PublicationCorresponds to variant dbSNP:rs34210653Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05668146 – 84Missing in isoform 2. 1 PublicationAdd BLAST39

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M23892 mRNA Translation: AAA36182.1
U88317 Genomic DNA Translation: AAB49305.1
AK290309 mRNA Translation: BAF82998.1
AK316126 mRNA Translation: BAH14497.1
AY505111 Genomic DNA Translation: AAR84235.1
AC118754 Genomic DNA No translation available.
BC029032 mRNA Translation: AAH29032.1
U63384 Genomic DNA Translation: AAC52118.1
CCDSiCCDS11049.1 [P16050-1]
PIRiA31349
RefSeqiNP_001131.3, NM_001140.3 [P16050-1]
UniGeneiHs.73809

Genome annotation databases

EnsembliENST00000293761; ENSP00000293761; ENSG00000161905 [P16050-1]
ENST00000570836; ENSP00000458832; ENSG00000161905 [P16050-1]
ENST00000574640; ENSP00000460483; ENSG00000161905 [P16050-2]
GeneIDi246
KEGGihsa:246
UCSCiuc002fyh.4 human [P16050-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiLOX15_HUMAN
AccessioniPrimary (citable) accession number: P16050
Secondary accession number(s): A8K2P4
, B7ZA11, Q8N6R7, Q99657
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: January 23, 2007
Last modified: May 23, 2018
This is version 182 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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